When bone integrity is threatened by trauma, infection, congenital malformation, tumor growth or degenerative diseases, a method of regenerating and healing the affected bone is the use of bone grafts. Bone grafts function in a manner similar to cancellous bone—supporting new tissue growth by providing the bone and blood cells with a matrix through which to interweave, as they reconnect the bone fragments.
There are three processes that are characteristic of a successful bone graft.                (1) osteoconduction—the apposition of growing bone to the three-dimensional surface of a suitable scaffold provided by the graft;        (2) osteoinduction—the biologically mediated recruitment and differentiation of cell types essential for bone; and        (3) osteogenesis—the process of bone formation through cellular osteoblastic activity and remodeling through osteoclastic activity, which, in turn, is dependent upon the presence of osteoprogenitor stem cells.        
Orthopedists in this field currently use a variety of materials when attempting to enhance these three processes. A sampling of these materials include the autograft, cadaveric allograft, xenograft, and several types of graft materials. These materials are considered basic types of bone substitutes that are used alone and sometimes in combination.
Autogenous bone is generally widely used in this field. Autogenous bone grafts, or autografts, have a number of advantages. They are histocompatible, they do not transfer disease and they retain viable cells that contribute to the formation of new bone including osteoblasts. Histocompatibility, for example, allows the cellular reaction that accompanies implantation to proceed without an immunologic rejection of the graft, and the graft generally integrates well into the graft site. Autografts can be prepared from cancellous bone or cortical bone. However, the latter material typically lacks the porosity required for cellular migration and revascularization.
The anterior or posterior aspect of the iliac crest provides a common donor site from which to harvest autograft material. Donor material from the iliac crest provides osteogenic properties in the form of surviving osteogenic precursor cells. The loose trabecular structure of the iliac crest encourages ingrowth of blood vessels that are necessary to support bone growth by helping to reduce ischemic necrosis of cellular elements. The noncollagenous bone matrix proteins of the iliac crest include growth factors and also provide osteoinductive properties. The bone mineral and collagen in the autograft material transplanted from the iliac crest provide a compatible osteoconductive surface.
Unfortunately, the full potential of autografts are not fully realized in practice because graft processing results in the death of much of the cellular elements. Those cells that survive must initially receive their oxygen via diffusion. Thus, considerable anoxic cell death probably occurs before sufficient vascularization has permeated the graft. Revascularization into the internal regions of the autograft is slow and incomplete and can be inhibited by fibrin clotting in the autograft and by the packing procedure used to place the graft into the surgical site. Packing of the autograft into a surgical site can decrease the porosity of the graft, in turn decreasing the potential for revascularization of the innermost areas of the graft. Cell death in the autograft leaves behind only a bone mineral scaffold.
Among several other shortcomings, the harvesting process of autograft is high in cost. Other shortcomings include the limited quantity of bone available for harvest, significant donor-site morbidity (rates as high as 25%), temporary disruption of donor-site bone structure, complications such as infection and pain, increased operative time and significantly increased operative blood loss. Minor complications include superficial infection and seromas, and minor hematomas. More serious complications include herniation of abdominal contents through massive bone graft donor sites, vascular injuries, deep infections at the donor site, neurologic injuries, deep hematoma formation requiring surgical intervention and iliac wing fractures.
Autograft alternatives include allografts, xenografts and synthetic bone grafts. Allografts are bone grafts harvested from a human donor other than the recipient. They are usually cleaned and processed to remove cells and debris to minimize their potential for eliciting an immune response or to carry infectious agents. Such tissue can be preserved by processes that can compromise mechanical properties like freeze-drying or freezing. As a result of this processing, allografts do not contain living cells and are not osteogenic. Although their properties vary with preparation methods, they generally have osteoconductive properties and can exert a somewhat stimulatory (osteoinductive) effect on cell in-migration and differentiation.
Xenografts are harvested from animals. Because of their immunogenicity, xenografts harvested from another species have generally been impractical for clinical use. Removal of proteinaceous and fatty materials during processing, as is done in the preparation of Kiel bone, or Oswestry bone, reduces immunogenicity. However, the processing required to produce this type of graft removes the osteoinductive matrix proteins. To guarantee viral inactivation, not only cells, but all proteins must be removed, thus eliminating both osteogenic and osteoinductive potential.
As a result, alternative bone-grafting strategies have been investigated. The development of composite grafts that combine synthetic cancellous bone void fillers with autogenous bone-forming cells could simplify and improve grafting procedures.
Accordingly, there is a need to provide methods of preparing a biologically active composite material that is osteoconductive, and at least osteoinductive or osteogenic.
There is a need to provide biologically active composite materials that are made of porous inorganic material and an infiltrant.
There is a need to provide methods for restoring an osseous void for situations requiring the use of a bone void filler for filling voids or gaps.
There is a need to provide methods to fill spaces between two bony structures to allow fusion, such as between the vertebral bodies of the spine.
There is a need to provide kits needed to create the biologically active composite, deliver the composite mass into a void, and therefore restore an osseous void.